JPS014

HCT116 human colon carcinoma cells

0.1, 1, 10 μM (24 h); 10 μM (48 h)

24 h (0.1, 1, 10 μM); 48 h (10 μM)

Induced degradation of HDAC1, HDAC2, and HDAC3 at 0.1, 1, and 10 μM for 24 h, with HDAC3 degradation significantly enhanced at 1 μM compared to PROTAC 1 (JPS004).
Increased H3K56ac levels to comparable or greater levels than HDAC inhibitor CI-994 and PROTAC 1.
Reduced SIN3A levels to 50% of control abundance after 24 h at 10 μM.
Significantly reduced LSD1 levels compared to DMSO and CI-994 controls after 48 h at 10 μM.
Exhibited a hook effect for HDAC3 at concentrations greater than 1 μM, where HDAC3 abundance increased rather than decreased, while HDAC1/2 levels continued to decrease.
Achieved degradation DC₅₀ values of 0.91 μM for HDAC1, 4.19 μM for HDAC2, and 0.64 μM for HDAC3, with maximal degradation (Dmax) values of 74% for HDAC1, 56% for HDAC2, and 59% for HDAC3.
Showed submicromolar inhibitory activity against purified HDAC complexes, with IC₅₀ values of 0.22 μM for HDAC1-CoREST, 0.36 μM for HDAC2-CoREST, and 0.14 μM for HDAC3-SMRT.

HCT116 human colon carcinoma cells

10 μM

24 h ; 48 h

Caused a substantial percentage of cells to enter the sub-G1 phase, indicating significant apoptosis after 24 h at 10 μM.
Induced sub-G1 population levels comparable to PROTAC 1 and CI-994 after 48 h at 10 μM.
Reduced cell viability with an EC₅₀ of 7.3 μM after 48 h.